The sense of smell contributes significantly to human life. Odors cue strong context-specific memories and play an important role in one's ability to sense and respond to both pleasant and noxious stimuli. Cyclic nucleotide-gated channels (CNGCs) in the dendritic cilia of olfactory receptor neurons (ORNs) are a critical component of the process by which sensory transduction occurs. The role of CNGCs expressed in the axons and synaptic terminals of ORNs is much less clear. [unreadable] [unreadable] The primary objective of this proposal is to examine modulation of synaptic transmission between ORNs and neurons in the olfactory bulb by cyclic nucleotides and CNGCs. To do this, neurons that receive synaptic input from the olfactory nerve will be whole cell patch clamped. The first aim is to determine whether raising the intracellular concentration of cyclic nucleotides modulates olfactory nerve-mediated synaptic transmission in a CNGC-dependent manner. Next the precise mechanism by which activation of CNGCs regulates neurotransmitter release will be examined. The final specific aim seeks to identify endogenous signaling mechanisms in the bulb that contribute to CNGC-dependent modulation. These experiments will provide a more complete understanding of how CNGCs contribute to olfactory processing. Moreover, the proposed research will help address how deficits in CNGC-dependent signaling lead to olfactory processing errors.